{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:26:14Z","timestamp":1791390374828,"version":"4.3.3"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32141001, 81802043, 81902102, 81830069"],"award-info":[{"award-number":["32141001, 81802043, 81902102, 81830069"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Colistin and tigecycline are usually regarded as the last resort for multidrug-resistant <jats:italic>Klebsiella pneumoniae<\/jats:italic> infection treatment. Emergence of colistin and tigecycline resistance poses a global healthcare challenge and is associated with high mortality due to limited therapeutic options. Here, we report the ST656 extensively drug-resistant <jats:italic>K. pneumoniae<\/jats:italic> strain KP15-652, which was isolated from a patient\u2019s urine in China. Antimicrobial susceptibility testing showed it to be resistant to tigecycline, amikacin, levofloxacin, ciprofloxacin, and high-level colistin resistance (&amp;gt; 2048 mg\/L). Whole-genome sequencing revealed that it harbors one chromosome and seven plasmids, including four plasmids carrying multiple acquired resistance genes. Transformation\/conjugation tests and plasmid curing assays confirmed that <jats:italic>mcr-1.1<\/jats:italic>, <jats:italic>mcr-8.2<\/jats:italic> and <jats:italic>crrB<\/jats:italic> mutations are responsible for the high-level colistin resistance and that a series of efflux pump genes, such as <jats:italic>tmexCD1-toprJ1<\/jats:italic>, <jats:italic>tet<\/jats:italic>(A) and <jats:italic>tet<\/jats:italic>(M), contribute to tigecycline resistance. <jats:italic>mcr-1.1<\/jats:italic> and <jats:italic>tet<\/jats:italic>(M) are located on an IncX1 plasmid, which has conjugation transfer potential. <jats:italic>mcr-8.2<\/jats:italic> and <jats:italic>tet<\/jats:italic>(A) are located on a multireplicon IncR\/IncN plasmid but unable to be transferred <jats:italic>via<\/jats:italic> conjugation. Moreover, another conjugable and fusion plasmid carries the <jats:italic>tmexCD1-toprJ1<\/jats:italic> gene cluster, which may have arisen due to IS<jats:italic>26<\/jats:italic>-mediated replicative transposition based on 8-bp target-site duplications. Importantly, a complex class 1 integron carrying various resistance genes was detected on this fusion plasmid. In conclusion, it is possible that the high-level of colistin resistance is caused by the accumulated effect of several factors on the chromosome and <jats:italic>mcr<\/jats:italic>-carrying plasmids, combined with many other resistances, including tigecycline. Effective surveillance should be performed to prevent further dissemination.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1122532","type":"journal-article","created":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T09:16:27Z","timestamp":1674724587000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Emergence of high-level colistin resistance mediated by multiple determinants, including mcr-1.1, mcr-8.2 and crrB mutations, combined with tigecycline resistance in an ST656 Klebsiella pneumoniae"],"prefix":"10.3389","volume":"13","author":[{"given":"Yanfei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5561","DOI":"10.1128\/AAC.00547-15","article-title":"The ribosomal S10 protein is a general target for decreased tigecycline susceptibility","volume":"59","author":"Beabout","year":"2015","journal-title":"Antimicrob. 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